1) Mood Disorders
Mood disorders refers to states in which mood (emotional) disturbances that persist over a certain period of time cause pain to be felt or present with some trouble in everyday life; they are symptoms found in mental disorders such as depression and manic-depressive illness. Depression that presents with only symptoms of depression and manic-depressive illness in which episodes of mania alternate with episodes of depression are two most typical examples. While various factors have been proposed as causes of mood disorders, most remain unclear about details.
2) Herpes Virus
Viruses of the family Herpesviridae are such that a core protein is surrounded by double-stranded DNA with molecular masses of 80-150×106 Daltons that is enclosed in an icosahedral capsid with a diameter of about 100 nm that consists of 162 capsomers to form a nucleocapsid which is surrounded by an envelope to have an overall size of ca. 150-200 nm. Herpes viruses have been found in almost all mammals and amphibians and, in particular, viruses of the family Herpesviridae that have host specificity for humans are named human herpesviruses (HHVs). HHVs are classified into subfamilies Alpha herpesvirinae (e.g., herpes simplex virus and varicella zoster herpes virus), Beta herpesvirinae (e.g., cytomegalovirus), and Gamma herpesvirinae (e.g., EB virus).
These herpes viruses can pass through four stages of their life cycle, cell infection, latent infection, proliferation, and reactivation. “Latent infection” refers to such a state of infection that a virus that has infected a host cell will not produce infectious virions within the host cell but continues to survive. Even in this phase of latent infection, the virus genes and the gene products that help them to exist are retained within the host cell. Herpes viruses that exhibit latent infection are known to resume viral replication and produce large amounts of virions owing to certain causes on the side of the host (e.g., aging and somatic complaints (including fatigue)). This state is called “reactivation.” In addition, the “proliferation” of a virus refers collectively to such stages that the virus increases the numbers of its genes and virions.
In short, herpes viruses have such a unique character that they continue to infect the host latently as long as it has nothing abnormal but that once a somatic disturbance occurs in the host and the virus detects that the host is in danger, it is reactivated to seek another, healthy host.
To study the biology of such viruses of the family Herpesviridae, understanding their latent infection and reactivation is essential. However, among the many herpes viruses, it is only EB virus which belongs to the subfamily Gamma herpesvirinae that has been studied to yield many findings about latent infection and much remains unclear about other viruses.
In particular, concerning factors that may be involved in the latent infection of Beta herpesvirinae, there has been obtained no information other than from the findings previously published by the present inventors. For example, Non-Patent Document 1 discloses latent infection of HHV-6 in macrophages in peripheral blood that have differentiated to a fairly high extent and identifies the sites in a host at which it is latently infected with HHV-6. Non-Patent Document 2 describes very frequent invasion of HHV-6 into the brain upon primary infection to cause persistent infection and latent infection. Non-Patent Document 3 discloses genes (latent infection genes) that are expressed during latent infection of HHV-6 and it suggests that those genes play the role of regulating the latent infection and reactivation of the virus.
Non-Patent Document 4 shows that the state of latent infection with HHV-6 involves an intermediate stage which is comparatively stable and allows for active gene expression, with the result that a latent infection gene and a protein encoded by this gene (the latent infection gene protein) are expressed abundantly. What is more, Non-Patent Document 5 shows that patients with chronic fatigue syndrome had in their sera antibodies to latent infection gene proteins the expression of which is enhanced at the intermediate stage.
The chronic fatigue syndrome (CFS) as used herein is a disease that causes severe fatigue to be felt for at least six months with no distinct reason and the diagnostic criteria for CFS are as follows: 1. The state where the patient has to miss several days of work or school a month on account of the disabling fatigue that is felt persists or relapses for at least six months; and 2. No other diseases are suspected. The symptoms of CFS include: (1) slight fever or chills; (2) sore throat; (3) swollen lymph nodes; (4) weakness of unknown cause; (5) muscle pain; (6) general feeling of malaise; (7) headache; (8) joint pain; (9) psychoneurotic symptoms; (10) sleep disorders; (11) sudden onset; the diagnosis is confirmed if at least eight of these symptoms are recognized (Non-Patent Document 5). It should be noted here that CFS is categorized as a different disease from mood disorders and a diagnosis of CFS is rejected if bipolar I disorders (manic-depressive illness and bipolar depression) are suspected. Finally, Non-Patent Document 6 describes a case in which patients who were presenting with encephalitis/encephalopathy-like symptoms and long-standing fatigue symptoms, presumably due to the infection with HHV-6 or Epstein-Barr virus (EBV), were administered with the anti-herpes viral agent valganciclovir, with the result that 75% of the patients had their symptoms improved.    Non-Patent Document 1: Kondo, K., et al. Latent human herpesvirus 6 infection of human monocytes/macrophages (J Gen Virol 72:1401-1408, 1991)    Non-Patent Document 2: Kondo, K., et al. Association of human herpesvirus 6 infection of the central nervous system with recurrence of febrile convulsions. (J Infect Dis 167:1197-1200, 1993)    Non-Patent Document 3: Kondo, K., et al. Identification of human herpesvirus 6 latency-associated transcripts. (J Virol. 76: 4145-4151, 2002)    Non-Patent Document 4: Kondo, K., et al. Recognition of a Novel Stage of Beta-Herpesvirus Latency in Human Herpesvirus 6. (J Virol. 77: 2258-2264, 2003)    Non-Patent Document 5: Kondo, K.; “Herupesu uirus kansen to hirou (Infection with Herpes Viruses and Fatigue)” in Virus, Vol. 55, No. 1, pp. 9-17, 2005    Non-Patent Document 6: Montoya, J. G., et al. (J Cli Virol. 2006 December; 37 Suppl:S33-8).